We have molecularly cloned and characterized ets genes from a sea urchin (Lytechinus variegatus) and the frog Xenopus laevis. Previously, we characterized a sea urchin gene with a high degree of similarity to vertebrate ets genes (Chen et al., Dev Biol 1988;125:432-40). We have recently sequenced a portion of another ets-hybridizing molecular clone from the same sea urchin species and determined it had a higher degree of similarity to the human ERG gene than to any of the canonical ets genes and thus represents the sea urchin ERG homolog. This implies that the ERG gene existed as a distinct entity prior to the divergence of the vertebrates and the echinoderms, an event that occurred at least 600 million years ago. We have characterized a molecular clone of the Xenopus laevis ets-2 gene that was isolated from an oocyte cDNA library. We have observed that injection of antisense oligonucleotides homologous to the ets-2 sequence into oocytes led to degradation of the mRNA and blocked hormone-induced germinal vesicle breakdown. The ets-2 product is thus required for the meiotic maturation of Xenopus oocytes. The interrelationships of the various canonical ets genes and ets-related genes were studied by use of several phylogenetic analysis procedures. This analysis suggested that the ets-1 and ets-2 genes diverged either very early in vertebrate evolution or before the emergence of this group, and confirmed that the canonical ets genes form a tight cluster in relation to the other genes. The C region of the human ELK1 gene appears to be more homologous to the Drosophila ets-related ecdysone-induced puff 74E gene than to any other gene. These genes may share a precursor that was already distinct from canonical ets in an organism that was ancestral to both Drosophila and vertebrates.